This study involved cerebroprotective potential of aloe emodin (AE) by in silico molecular docking analysis against various cerebrotoxic proteins followed by in vivo activity on multiple occlusions and reperfusion of bilateral carotid arteries (MO/RCA) induced cerebral injury in experimental rats. Molecular docking studies were carried out to evaluate the binding affinity (or binding interaction) between AE and various proteins involved in apoptosis such as caspase-3 (CASP3) and Bcl-2-associated X protein (BAX), and proteins involved in inflammation such as interleukin-6 (IL-6), tumor necrosis factor α (TNF α), nitric oxide synthase (NOS), acid-sensing ion channel (ASIC) and glutamate receptor (GR) involved in cerebral stroke, and results were compared with that of standard drugs, minocycline, quercetin, and memantine. Cerebral ischemic reperfusion induced by MO/RCA was assessed for 10 mins reperfusion period as one cycle, and the experiment was conducted for up to 3 cycles in rats. After completion of 3 cycles, the rats were subjected to ethically acceptable animal euthanasia followed by isolation of the brains which were studied for the size of cerebral infarction, and biochemical parameters such as glutathione (GSH), malondialdehyde (MDA), catalase (CAT) were estimated from the brain homogenate. Further, histological studies were done to study neuronal contact. Results of molecular docking indicated that the AE exhibited interaction with active sites of cerebrotoxic proteins usually involved in protein functions or cerebrotoxicity. Biochemical results showed that in the untreated brain, MDA levels increased significantly, and decreased GSH and CAT levels were observed when compared to MO/RCA group, while treated rats showed a decrease in the levels of MDA and an increase in GSH and CAT levels as compared to MO/RCA rats. In comparison with sham rats and normal rats, histopathological analysis revealed neuronal damage in MO/RCA surgery rats which manifested as decreased intact neurons. However, treatment with AE 50 mg/kg b.wt. restored contact between neuronal cells. It can be concluded that AE showed cerebroprotective effect on RO/RCA with promising inhibition of cerebrotoxic proteins (apoptotic and neuroinflammatory) as evident from molecular docking studies. The cerebroprotective potential of AE could be due to its anti-inflammatory, antioxidant, and antiapoptotic principles.

Cancer is one of the leading diseases, causing deaths worldwide. Nearly 10 million deaths were reported in 2020 due to cancer alone. Several factors are involved in cancer progressions, such as lifestyle and genetic characteristics. According to a recent report, extracellular vesicles (EVs) are involved in cancer initiation, progression, and therapy failure. EVs can play a major role in intracellular communication, the maintenance of tissue homeostasis, and pathogenesis in several types of diseases. In a healthy person, EVs carry different cargoes, such as miRNA, lncRNA etc., to help other body functions. On the other hand, the same EV in a tumor microenvironment carries cargoes such as miRNA, lncRNA, etc., to initiate or help cancer progression at various stages. These stages may include the proliferation of cells and escape from apoptosis, angiogenesis, cell invasion, and metastasis, reprogramming energy metabolism, evasion of the immune response, and transfer of mutations. Tumor-derived EVs manipulate by altering normal functions of the body and affect the epigenetics of normal cells by limiting the genetic makeup through transferring mutations, histone modifications, etc. Tumor-derived EVs also pose therapy resistance through transferring drug efflux pumps and posing multiple drug resistances. Such EVs can also help as biomarkers for different cancer types and stages, which ultimately help with cancer diagnosis at early stages. In this review, we will shed light on EVs’ role in performing normal functions of the body and their position in different hallmarks of cancer, in altering the genetics of a normal cell in a tumor microenvironment, and their role in therapy resistance, as well as the importance of EVs as diagnostic tools.

Acetylcholinesterase (AChE) inhibition is a key element in enhancing cholinergic transmission and subsequently relieving major symptoms of several neurological and neuromuscular disorders. Here, the inhibitory potential of geraniol and its mechanism of inhibition against AChE were elucidated in vitro and validated via an in silico study. Our in vitro enzyme inhibition kinetics results show that at increasing concentrations of geraniol and substrate, Vmax did not change significantly, but Km increased, which indicates that geraniol is a competitive inhibitor against AChE with an IC₅₀ value 98.06 ± 3.92 µM. All the parameters of the ADME study revealed that geraniol is an acceptable drug candidate. A docking study showed that the binding energy of geraniol (−5.6 kcal mol⁻¹) was lower than that of acetylcholine (−4.1 kcal mol⁻¹) with AChE, which exhibited around a 12.58-fold higher binding affinity of geraniol. Furthermore, molecular dynamics simulation revealed that the RMSD of AChE alone or in complex with geraniol fluctuated within acceptable limits throughout the simulation. The mean RMSF value of the complex ensures that the overall conformation of the protein remains conserved. The average values of Rg, MolSA, SASA, and PSA of the complex were 3.16 Å, 204.78, 9.13, and 51.58 Ų, respectively. We found that the total SSE of AChE in the complex was 38.84% (α-helix: 26.57% and β-sheets: 12.27%) and remained consistent throughout the simulation. These findings suggest that geraniol remained inside the binding cavity of AChE in a stable conformation. Further in vivo investigation is required to fully characterize the pharmacokinetic properties, optimization of dose administration, and efficacy of this plant-based natural compound.

Background: Few studies discussed the prevalence of TTIs in Saudi donor blood samples. Thus, this study investigated the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), syphilis and malaria in such samples to determine the efficacy of conducting serological and NATs on blood donors at King Khalid General Hospital in Majmaah, Saudi Arabia. Methods: A total of 3028 donated blood units were collected from August 2015 to March 2017. Serum samples were screened for hepatitis B surface antigens (HBsAgs), HBsAbs, total anti-core antibodies (HBcAbs), HCV antigens and HIV Ab/Ag combinations. Additionally, plasma was screened for syphilis (TPHA) and HTLV. Samples were also tested for malaria with rapid malaria antigen tests. Finally, NATs were performed for the simultaneous direct detection of HBV, HCV and HIV in each sample. Results: Out of the 3028 blood samples, 10 (0.33%) reacted to HBsAgs; 12 (0.40%) reacted to HCV antigens; 4 (0.13%) reacted to HIV Ab/Ag combinations; 6 (0.20%) reacted to HTLV antibodies; 297 (9.81%) reacted to HBcAbs and 236 (7.80%) reacted to HBsAbs. Additionally, NATs showed that 14 (0.46%) reacted to NATHBV; 20 (0.66%) samples were reacted to NAT-HCV and 2 (0.07%) samples reacted to NAT-HIV. Finally, 16 (0.53%) were positive for syphilis. No samples were positive for malaria. Conclusions: The results indicated that NATs are more effective than serology tests for detecting TTIs. Moreover, correlations between standard serology tests and NATs indicated that using NATs could improve test sensitivities and decrease residual risks of TTIs and ensure safe blood transfusions. (C) 2018 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences.

Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by both glutamate binding and postsynaptic depolarization, facilitating Ca²⁺ entry upon activation. Therefore, they are now widely acknowledged as being essential targets for excitotoxicity issues. Molecular docking and molecular dynamics (MD) simulation analyses have demonstrated that nobiletin efficiently targets the binding pocket of the NMDA receptor protein and exhibits stable dynamic behavior at the binding site. In this study, five potential neuroprotectants, nobiletin, silibinin, ononin, ginkgolide B, and epigallocatechin gallate (EGCG), were screened against the glutamate NMDA receptors in humans via computational methods. An in silico ADMET study was also performed, to predict the pharmacokinetics and toxicity profile for the expression of good drug-like behavior and a non-toxic nature. It was revealed that nobiletin fulfills the criteria for all of the drug-likeness rules (Veber, Lipinski, Ghose, Muegge, and Egan) and has neither PAINS nor structural alerts (Brenks). In conclusion, nobiletin demonstrated a possible promising neuroprotectant activities compared to other selected phytochemicals. Further, it can be evaluated in the laboratory for promising therapeutic approaches for in vitro and in vivo studies.

Cell phones may be an ideal habitat for colonization by bacterial pathogens, especially in hot climates, and may be a reservoir or vehicle in transmitting nosocomial infections. We investigated bacterial contamination on cell phones of healthcare workers in three hospitals in Saudi Arabia and determined antibacterial resistance of selected bacteria. A questionnaire was submitted to 285 healthcare workers in three hospitals, and information was collected on cell phone usage at the work area and in the toilet, cell phone cleaning and sharing, and awareness of cell phones being a source of infection. Screening on the Vitek 2 Compact system (bioMérieux Inc., USA) was done to characterize bacterial isolates. Of the 60 samples collected from three hospitals, 38 (63.3%) were positive with 38 bacterial isolates (4 Gram-negative and 34 Gram-positive bacteria). We found 38.3% of cell phones were contaminated with coagulase-negative staphylococci, particularly Staphylococcus epidermidis (10 isolates). Other bacterial agents identified were S. aureus, S. hominis, Alloiococcus otitis, Vibrio fluvialis, and Pseudomonas stutzeri. Antimicrobial susceptibility testing showed that most coagulase-negative staphylococci were resistant to benzylpenicillin, erythromycin, and rifampicin. Eight isolates were resistant to oxacillin, specifically S. epidermidis (3), S. hominis (2), and S. warneri (2). A. otitis, a cause of acute otitis media showed multidrug resistance. One isolate, a confirmed hetero-vancomycin intermediate-resistant S. aureus, was resistant to antibiotics, commonly used to treat skin infection. There was a significant correlation between the level of contamination and usage of cell phone at toilet and sharing. Our findings emphasize the importance of hygiene practices in cell phone usage among healthcare workers in preventing the transmission of multidrug-resistant microbes.